Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation

Zhao, Qi; Pavanello, Lorenzo; Bartlam, Mark; Winkler, Gerlof Sebastiaan

doi:10.3389/fgene.2023.1233842

Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation

Zhao, Qi; Pavanello, Lorenzo; Bartlam, Mark; Winkler, Gerlof Sebastiaan

Authors

Qi Zhao

Lorenzo Pavanello

Mark Bartlam

SEBASTIAAN WINKLER SEBASTIAAN.WINKLER@NOTTINGHAM.AC.UK
Associate Professor

Abstract

In eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5′cap structure and 3′poly(A) tail. These elements promote translation and prevent non-specific degradation. Degradation via the deadenylation-dependent 5′-3′ degradation pathway can be induced by trans-acting factors binding the mRNA, such as RNA-binding proteins recognising sequence elements and the miRNA-induced repression complex. These factors recruit the core mRNA degradation machinery that carries out the following steps: i) shortening of the poly(A) tail by the Ccr4-Not and Pan2-Pan3 poly (A)-specific nucleases (deadenylases); ii) removal of the 5′cap structure by the Dcp1-Dcp2 decapping complex that is recruited by the Lsm1-7-Pat1 complex; and iii) degradation of the mRNA body by the 5′-3′ exoribonuclease Xrn1. In this review, the biochemical function of the nucleases and accessory proteins involved in deadenylation-dependent mRNA degradation will be reviewed with a particular focus on structural aspects of the proteins and enzymes involved.

Citation

Zhao, Q., Pavanello, L., Bartlam, M., & Winkler, G. S. (2023). Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation. Frontiers in Genetics, 14, Article 1233842. https://doi.org/10.3389/fgene.2023.1233842

Journal Article Type	Article
Acceptance Date	Sep 25, 2023
Online Publication Date	Oct 9, 2023
Publication Date	Oct 9, 2023
Deposit Date	Dec 11, 2023
Publicly Available Date	Dec 12, 2023
Journal	Frontiers in Genetics
Electronic ISSN	1664-8021
Publisher	Frontiers Media
Peer Reviewed	Peer Reviewed
Volume	14
Article Number	1233842
DOI	https://doi.org/10.3389/fgene.2023.1233842
Keywords	gene expression, RNA decay, RNA, poly(A), nuclease, RNA degradation pathway, deadenylase complex
Public URL	https://nottingham-repository.worktribe.com/output/26792126
Publisher URL	https://www.frontiersin.org/articles/10.3389/fgene.2023.1233842/full